ProjectSummary/Abstract: Thecurrentlandscapeofoncologydrugdevelopmentisposingachallengetowidely-accepted methodsusedinearly-phaseclinicaltrials.AchallengeinPhaseItrialsofcancertreatmentis determiningarecommendedPhaseIIdose(RP2D)forfurthertestingofadoptivecelltherapies. Inthesetherapies,itmaynotbefeasibletoadministerapatient?sassigneddoseduetoan insufficientnumberofcellsharvestedorfunctionalheterogeneityoftheproduct.Thismakesit difficulttoidentifyafeasibledosetocarryforwardintomiddleandlatedevelopment,hindering theevaluationofthetherapeuticintervention.Accepteddosefindingdesignsweredeveloped foruseintrialsinwhichsuccessivepatientcohortsaretreatedatvariousdoselevelsthatare selectedbasedonthesafetydatafrompreviouscohorts.Thisapproachwasappropriateinthe historicalparadigminwhicheachpatientisabletoreceivehisorherintendeddosebasedon thedose-findingalgorithm.Inadoptivecelltherapy,thenumberofcellsproducedmaybebelow theassignedinfusiondoseidentifiedbythedose-findingdesignforagivenpatient.Thisraises questionsofhowtoassessthefeasibilityoftheapproach,whilealsoevaluatingsafety. Integratingaccumulatedfeasibilityandsafetydatatoselectsequentialdosesforpatientcohorts duringdose-findingtrialsremainsachallenge.Thereisneedtodevelopdosefindingdesignsfor adoptivecelltherapythatutilizefeasibilitydatainguidingallocationanddeterminingamaximum toleratedandfeasibledose(MTFD),leadingtomoreoptimaldosingandimprovedpatient outcomes.Theoverallgoalofthisproposalistodevelopdose-findingmethodologyforadoptive celltherapythatformallyintegratesdosefeasibilityintothedesign.